The proposal is divided into (1) study of the participation of the effector principles of IgE-mediated reactions and of the complement system in the dermatologic disorders cutaneous necrotizing angiitis, atopic eczema, bullous pemphigoid, and certain physical urticarias; and (2) characterization of the immunologic release of mast cell-derived mediators from human skin slices. Functional and immunochemical assessments of serum complement factors and morphologic tissue studies using the 1-micron-thick section technique will be performed. Further, activation of the complement system by cryoglobulins of different types will be studied in vitro. The release of histamine and chemotactic factors in vivo will be sought after appropriate challenge in patients with physical urticaria. Modulation of the clinical symptom complex with various therapeutic agents will be attempted. A recently recognized neutrophil chemotactic factor obtained from serum of patients with cold-induced urticaria will be characterized. The antigen-induced release of mediators from sensitized human skin slices will be studied; an attempt will be made to obtain cells in isolated suspensions from skin. The chemotactic capacity of synthetic ECF-A tetrapeptides in guinea pig skin will be studied in vitro, and attempts to use experimental bullae to study the cellular response to chemotactic mediators will be made in human skin.